Granted Patent B2

US 12,453,745 · App. 18/332,063 · Granted Oct 28, 2025

Inventors: Evangelos V. Badiavas (Coral Gables, FL); Arsalan Q. Shabbir (Miami, FL); Stephen C. Davis (El Portal, FL)

Assignee: UNIVERSITY OF MIAMI

A61K35/28A61K8/981A61K8/983A61K35/12A61K35/16A61K35/22A61Q19/00A61Q19/08A61K2800/74A61K2800/86

Abstract

Claims (27)

1. A topical composition for treating wounds comprising an aqueous concentrate of a heterogeneous population of purified, intact microvesicles,

wherein the intact microvesicles range in size from 2 nm to 5000 nm,

wherein the intact microvesicles have smooth and uncorrugated borders and appear intact when examined by electron microscopy, and

wherein the intact microvesicles enhance tissue regeneration, promote wound healing, enhance nerve growth, remodel scarred tissue, modulate immune reactions, alter neoplastic cell growth, and/or decrease abscess formation of a tissue when administered to a patient.

2. The composition of claim 1 , wherein the tissue is selected from the group consisting of epithelial tissue, stromal tissue, nerve tissue, vascular tissue, and adnexal tissue.

3. The composition of claim 1 , wherein the tissue is a tissue wound.

4. The composition of claim 3 , wherein the tissue wound is a burn.

5. The composition of claim 4 , wherein the burn is a full-thickness burn or a second-degree burn.

6. The composition of claim 1 , wherein the intact microvesicles comprise ectosomes, exosomes, microparticles, microvesicles, nanovesicles, shedding vesicles, apoptotic bodies, and/or membrane particles.

7. The composition of claim 1 , wherein the intact microvesicles express the exosomal markers HSP 70, CD63, and/or STAT3.

8. The composition of claim 1 , wherein the intact microvesicles range in size from 2 nm to 200 nm.

9. The composition of claim 1 , wherein the intact microvesicles have a molecular weight of at least 100 kDa.

10. The composition of claim 1 , wherein the polyethylene glycol comprises a molecular weight from about 200 Da to about 10,000 Da.

11. The composition of claim 1 , wherein the polyethylene glycol comprises a molecular weight from about 200 Da to about 8,000 Da.

12. The composition of claim 1 , wherein the polyethylene glycol comprises a molecular weight greater than 10,000 Da.

13. The composition of claim 1 , wherein the polyethylene glycol comprises a concentration from about 0.5% w/v to about 100% w/v.

14. The composition of claim 1 , wherein the polyethylene glycol comprises a concentration from about 5% w/v to about 25% w/v.

15. The composition of claim 1 , wherein the biological fluid is treated with at least one agent comprising an anti-inflammatory compound, an anti-apoptic compound, an inhibitor of fibrosis, a compound that is capable of enhancing angiogenesis, an immunosuppressive compound, a compound that promotes survival of cells, a chemotherapeutic, a compound capable of enhancing cellular migration, a neurogenic compound, and a growth factor.

16. The composition of claim 1 , wherein the biological fluid comprises blood, sera, plasma, ascites, urine, cerebrospinal fluid, sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, broncheoalveolar lavage fluid, semen, Cowper's fluid, female ejaculate, sweat, fecal matter, hair, tears, cyst fluid, pleural and peritoneal fluid, pericardial fluid, lymph, chyme, chyle, bile, interstitial fluid, menses, pus, sebum, vomit, vaginal secretions, mucosal secretions, stool water, pancreatic juice, lavage, or aspirates.

17. The composition of claim 1 , wherein the biological fluid is pre-treated prior to collection of the microvesicles by adding at least one agent comprising interleukin, VEGF, transcription factors, hormones, neurotransmitters, pharmaceuticals, liposomes, transfecting agents or by exposing the biological fluid to altered physical conditions including hypoxia, cold shock, and/or heat shock.

18. The composition of claim 14 , wherein the growth factor comprises a member of the TGF-β family, bone morphogenic proteins, fibroblast growth factors, platelet-derived growth factor, platelet rich plasma, insulin growth factor, growth differentiation factor, vascular endothelial cell derived growth factor, pleiotrophin, endothelin, and mixtures thereof.

19. The composition of claim 17 , wherein the pharmaceutical comprises nicotinamide, hypoxia inducible factor 1-alpha, glucagon like peptides, extendins, nodal, noggin, NGF, retinoic acid, parathyroid hormone, tenascin-C, tropoelastin, thrombin-derived peptides, cathelicidins, defensins, laminin, biological peptides, MAPK inhibitors, and mixture thereof.

20. A method of treating a tissue wound in a patient in need thereof, the method comprising administering an effective amount of the composition of claim 1 to the tissue wound of the patient.

21. The method of claim 20 , wherein the administration is done topically or by injection.

22. The method of claim 21 , wherein the injection is a local injection.

23. The composition of claim 20 , wherein wrinkle formation or scar formation is reduced in the treated tissue wound of the patient.

24. The composition of claim 20 , wherein the composition does not provoke a significant inflammatory response in the tissue wound of the patient.

Assignments (1)

Continuity (4)

References Cited (165)